Triethyloxonium tetrafluoroborate → {(S)-1-[6-Fluoro-1-(5-fluoropyridin-3-yl)-1H-benzoimidazol-2-yl]propyl}carbamic acid tert-butyl ester

HRID 243178Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 243178
[C:1]([O:5][C:6](=[O:14])[NH:7][C@H:8]([C:11](=O)[NH2:12])[CH2:9][CH3:10])([CH3:4])([CH3:3])[CH3:2].F[B-](F)(F)F.C([O+](CC)CC)C.[F:27][C:28]1[CH:29]=[C:30]([NH:35][C:36]2[CH:37]=[N:38][CH:39]=[C:40]([F:42])[CH:41]=2)[C:31](N)=[CH:32][CH:33]=1>C(Cl)Cl>[C:1]([O:5][C:6](=[O:14])[NH:7][C@H:8]([C:11]1[N:35]([C:36]2[CH:37]=[N:38][CH:39]=[C:40]([F:42])[CH:41]=2)[C:30]2[CH:29]=[C:28]([F:27])[CH:33]=[CH:32][C:31]=2[N:12]=1)[CH2:9][CH3:10])([CH3:4])([CH3:3])[CH3:2]

Komponenten

5

Edukt 3

HCID 2723982Triethyloxonium tetrafluoroborateHCID 45092008tert-Butyl (S)-(1-amino-1-oxobutan-2-yl)carbamateHCID 681580564-Fluoro-N2-(5-fluoropyridin-3-yl)benzene-1,2-diamine

Produkt 1

HCID 68157999{(S)-1-[6-Fluoro-1-(5-fluoropyridin-3-yl)-1H-benzoimidazol-2-yl]propyl}carbamic acid tert-butyl esterAusbeute 82,4 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 6344DichloromethaneLösungsmittel

Versuchsvorschrift

To a suspension of ((S)-1-carbamoylpropyl)carbamic acid tert-butyl ester (250 mg, 1.24 mmol) in DCM (5 mL) was added triethyloxonium tetrafluoroborate (228 mg, 1.20 mmol) and the reaction mixture stirred at RT for 1.5 h under argon. The reaction mixture was concentrated in vacuo and the residue dissolved in ethanol (3 mL). 4-Fluoro-N2-(5-fluoropyridin-3-yl)benzene-1,2-diamine (88 mg, 0.40 mmol) was added and the reaction mixture heated at 60° C. for 20 min. The reaction mixture was concentrated in vacuo, and the residue partitioned between DCM and sat. NaHCO3. The organic fraction was washed with brine, dried (Na2SO4) and concentrated in vacuo. The resultant residue was subjected to flash chromatography (Si—PPC, gradient 0-50% EtOAc in cyclohexane) to afford the title compound as a white foam (128 mg, 82%). LCMS (Method J): RT=3.42 min, [M+H]+=389.

Aufarbeitung

  1. concentrationThe reaction mixture was concentrated in vacuo
  2. dissolutionthe residue dissolved in ethanol (3 mL)
  3. temperaturethe reaction mixture heated at 60° C. for 20 min
  4. concentrationThe reaction mixture was concentrated in vacuo
  5. customthe residue partitioned between DCM and sat. NaHCO3
  6. washThe organic fraction was washed with brine
  7. dry with materialdried (Na2SO4)
  8. concentrationconcentrated in vacuo

Quellen und Nachweise

ORD-Eintrag
ord-d1d93f16ecf442acb7cc0992b3dade8a
Quelldatensatz
uspto-grants-2014_02
Patentnummer
US08653089B2

Notizen zur Reaktion

Wird geladen…